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Association of the 276GT polymorphism of the adiponectin gene with cardiovascular disease risk factors in nondiabetic Koreans^1,2,3

¹ From the Division of Cardiology, Cardiovascular Genome Center, Yonsei Medical Institute (YJ),the Yonsei University Research Institute of Science for Aging (YJ, JHL, JSC, OYK, SJK, JYK, and HC), and the Department of Food and Nutrition, College of Human Ecology (JHL), Yonsei University, Seoul, Korea; the DNA Link Corporation, Seoul, Korea (JEL); and the Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA (JMO)

Background: The adiponectin gene is known to modulate adiponectin concentrations and diabetes mellitus development.

Objective: We assessed whether adiponectin gene variants contribute to circulating adiponectin, insulin resistance (IR), or cardiovascular disease risk factors.

Design: Nondiabetic subjects [n = 902; ± SE age: 42.5 ± 0.53 y; body mass index (BMI; in kg/m²): 24.7 ± 0.11] were genotyped for 2 single-nucleotide polymorphisms (SNPs), 45TG and 276GT.

Results: After adjustment for age, sex, and BMI, subjects with the G allele for the SNP 276 had significantly higher concentrations of triacylglycerol and small dense LDL (sdLDL) and smaller LDL particle size than did T/T subjects. G/G subjects at SNP 276 had significantly lower plasma adiponectin and higher homeostasis model assessment (HOMA) of IR and urinary prostaglandin F2 than did T/T subjects. In the SNP 45-276 haplotype test, we also observed that subjects with the X/X haplotype had significantly higher plasma adiponectin after adjustment than did TG/TG or TG/X haplotype subjects. In the highest BMI group (BMI 26), T/T subjects had lower HOMA-IR (P = 0.011) and higher plasma adiponectin (P = 0.026) at SNP 276 than did G/G or G/T subjects. These patterns were also seen for adiponectin in haplotype groups. However, no significant genotype effect for SNP 45TG was observed.

Conclusions: The 276GT polymorphism of the adiponectin gene modulates circulating adiponectin and IR, particularly in obese states. G allele carriers also have higher oxidative stress, higher sdLDL concentrations, and smaller LDL particle size. Therefore, the presence of the G allele in the adiponectin gene at SNP 276 could be a significant contributor to higher cardiovascular disease risk in Koreans, independent of common environmental factors.

Key Words: Adiponectin • 267GT • obesity • insulin resistance • cardiovascular disease risk

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